OVERALL PROJECT SUMMARY/ABSTRACT This is a new application for a P30 ADRC at Columbia University, continuing the tradition of our previous P50 ADRC that has existed at Columbia since 1989. Building off our prior accomplishments, the overall objective of the new ADRC is to support and promote cutting-edge research on Alzheimer?s disease (AD) and related disorders, both locally in our extensive campus and more globally with other institutions and national consortia. Subsumed within this objective the Center will have a more focused theme. The theme, focusing on ?biological pathways? implicated in AD pathogenesis, was decided on after internal deliberations, discussions with our External Advisory Committee members, and with NIH project officers. As reviewed throughout the proposal, we believe that this broad theme has many advantages. It will strengthen the overall objective by better serving our local community of basic, translational, and clinical investigators; and will generate new tools and resources that we will share with other institutions, consortia, and organizations. Additionally, the theme will allow each core to have both general aims that harmonize with other ADRCs and consortia, and theme-guided aims that emerge from our local strengths. As reviewed below, the theme will allow cores to synergize and work together in creating a research infrastructure that relate to the clinical phenomenology, neuropathology, neuroimaging, and genomics of AD. Since its inception 30 years ago, the ADRC at Columbia has established an elaborate infrastructure for research, fostered interdisciplinary collaborations, established a rich training environment, and promoted outreach and patient recruitment. At the same time the Center has become an active participant in a more global network comprised of other institutions, national consortia, and community organizations. During the many cycles of the P50 ADRC, the Center has attained most of its goals, as evidenced, for example, by the breadth of its scientific findings and by its high ranking of enrolled and active patients. In this proposal for a new P30 ADRC we will build off of these prior accomplishments moving forward, and will be motivated by two general goals. The first goal is to continue, as in previous cycles, to foster all research on AD and related disorders, while the second goal is to support the theme. We propose to achieve these goals through our well-integrated cores, which collectively establishes an infrastructure that generates a rich array of resources, biospecimens, and expertise. Besides the Administrative Core, these cores include a Clinical Core led by Dr. Lawrence Honig, a ?Data Management and Statistical? Core led by Dr. Howard Andrews, a Neuropathology Core led by Dr. Andrew Teich, a Biomarker Core led by Dr. Adam Brickman, a Genetics Core led by Dr. Christiane Reitz, a Neuroimmunology Core led by Dr. Phillip De Jager, an ?Outreach, Retention, and Engagement? Core led by Dr. William (Ted) Huey, and a ?Research Education? Module led by Dr. James Noble.